The role of microbial pattern recognition mechanisms in bacterial-induced autophagy in the social amoeba Dictyostelium discoideum (INC7P.416)

Signaling downstream of innate immune pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), results in activation of various responses, including the induction of autophagy. Recent evidence suggests that autophagy plays a protective role against invading intracellular microbes. We have found that upon incubation with bacteria or with the microbial pattern LPS, autophagosomal maturation is stimulated in the model organism Dictyostelium discoideum , which uses bacteria for nutritional purposes. In addition, the rate of bacterial clearance by D. discoideum cells is increased upon exposure of cells to the autophagy-inducing drug rapamycin. Conversely, lysosomal transport of bacteria is decreased in D. discoideum lacking the autophagy protein, Atg1. Although the D. discoideum genome does not encode for TLRs, it does encode for a number of TIR (toll/interleukin-1 receptor) domain-containing proteins, including TirA. Cells lacking TirA are deficient in responses to Gram-negative bacteria. We have found here that TirA plays a role in bacterial-induced generation of reactive oxygen species, a potential stimulant of autophagy. We are investigating the role of TirA as well as the role of reactive oxygen species in pathogen-induced autophagy. These studies are aimed at linking microbial pattern recognition and the induction of autophagy in this model organism to provide insight into conserved mechanisms underlying bacterial detection.